The importance for research and clinical utility of mutation databases, as well as the issues and difficulties entailed in their construction, is discussed within the Human Variome Project. While general principles and standards can apply to most human diseases, some specific questions arise when dealing with the nature of genetic neurological disorders. So far, publically accessible mutation databases exist for only about half of the genes causing neurogenetic disorders; and a considerable work is clearly still needed to optimize their content. The current landscape, main challenges, some potential solutions, and future perspectives on genetic databases for disorders of the nervous system are reviewed in this special issue of Human Mutation on neurogenetics. Hum Mutat 33:1311–1314, 2012. © 2012 Wiley Periodicals, Inc.